PMID- 19477173 OWN - NLM STAT- MEDLINE DCOM- 20090928 LR - 20181201 IS - 1090-2422 (Electronic) IS - 0014-4827 (Linking) VI - 315 IP - 15 DP - 2009 Sep 10 TI - Modulation of DNA glycosylase activities in mesenchymal stem cells. PG - 2558-67 LID - 10.1016/j.yexcr.2009.05.017 [doi] AB - Adipose-tissue derived mesenchymal stem cells (AT-MSCs) are a promising tool for use in cell-based therapies. However, in vitro expansion is required to obtain clinically relevant cell numbers, and this might increase the chance of genomic instability. DNA repair is crucial for maintaining DNA integrity. Here we have compared the initial step of base excision repair in uncultured and cultured AT-MSCs by analysis of base removal activities and expression levels of relevant DNA glycosylases. Uracil, 5-hydroxyuracil and ethenoadenine removal activities were upregulated in cultured cells compared to uncultured cells. In contrast, both the 8-oxo-7,8-dihydroguanine (8-oxoG) removal activity and the concentration of 8-oxoG bases in the DNA were reduced in the cultured cells. Gene expression analysis showed no substantial changes in mRNA expression. The glycosylase activities remained stable through at least 12 passages, suggesting that DNA repair is proficient through the period required for in vitro expansion of AT-MSCs to clinically relevant numbers. FAU - Hildrestrand, Gunn A AU - Hildrestrand GA AD - Centre for Molecular Biology and Neuroscience and Institute of Medical Microbiology, Rikshospitalet University Hospital, Oslo, Norway. FAU - Duggal, Shivali AU - Duggal S FAU - Bjoras, Magnar AU - Bjoras M FAU - Luna, Luisa AU - Luna L FAU - Brinchmann, Jan E AU - Brinchmann JE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090525 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 496-76-4 (5-hydroxyuracil) RN - 5614-64-2 (8-hydroxyguanine) RN - 56HH86ZVCT (Uracil) RN - 5Z93L87A1R (Guanine) RN - EC 3.2.2.- (DNA Glycosylases) SB - IM MH - Adipose Tissue/cytology MH - Animals MH - Cells, Cultured MH - DNA Damage MH - DNA Glycosylases/genetics/*metabolism MH - *DNA Repair MH - Gene Expression Profiling MH - Guanine/analogs & derivatives/metabolism MH - Humans MH - Immunophenotyping MH - Mesenchymal Stem Cells/cytology/*physiology MH - Oligonucleotide Array Sequence Analysis MH - Uracil/analogs & derivatives/metabolism EDAT- 2009/05/30 09:00 MHDA- 2009/09/29 06:00 CRDT- 2009/05/30 09:00 PHST- 2009/02/02 00:00 [received] PHST- 2009/04/28 00:00 [revised] PHST- 2009/05/19 00:00 [accepted] PHST- 2009/05/30 09:00 [entrez] PHST- 2009/05/30 09:00 [pubmed] PHST- 2009/09/29 06:00 [medline] AID - S0014-4827(09)00226-2 [pii] AID - 10.1016/j.yexcr.2009.05.017 [doi] PST - ppublish SO - Exp Cell Res. 2009 Sep 10;315(15):2558-67. doi: 10.1016/j.yexcr.2009.05.017. Epub 2009 May 25.